A prospective survey was conducted in a random sample of smokers (SMO) and non-smokers (NON) men living in Havana. The aim of the survey was to investigate metabolic and dietary parameters discriminating between SMO and NON volunteers, which could explain underlying mechanisms to the higher risk of Epidemic Neuropathy (51,000 reported cases in Cuba from late 1991) previously demonstrated in the Cuban smoker. Forty three blood markers were determined and dietary intakes evaluated during 4 seasonal periods. alpha-carotene, beta-carotene, beta-cryptoxanthin, total carotenoids and riboflavin blood concentrations were lower in SMO vs. NON subjects. Activities of glutathione reductase and butryrylcholinesterase were lower in the SMO group, as did total protein levels. Copper and thiocyanates were higher in SMO subjects. Most of the dietary parameters did not differ between the two groups of volunteers. Low biologically available quantities of carotenoids and riboflavin from low dietary intakes and depletion through smoking would be the main precipitating factors of Epidemic Neuropathy. Protein depletion and copper delivery via tobacco smoke, sunlight exposure, level of physical activity and high consumption of cigarettes, in a context of low dietary supplies concerning especially B vitamins, were probably aggravating factors through oxidative stress and impairment of cyanide detoxification.